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Z. Fazreen
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-003 - Co-Expression of Programmed Death Ligand-1 (PD-L1) and CD3 in Patients with EGFR Mutant NSCLC Treated with EGFR Tyrosine Kinase Inhibitors (TKI) (ID 1163)
09:30 - 09:30 | Author(s): Z. Fazreen
- Abstract
Background:
Recent reports have suggested an association between non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) gene mutations. Other studies have indicated that EGFR signaling can activate PD-L1 expression and immune escape in mutant EGFR driven NSCLC. Furthermore PD-L1 expression is down-regulated by EGFR TKI. In this study, we aim to determine the association between tumoral and immune cell PDL1 expression and clinical characteristics and outcome in EGFR mutant NSCLC patients treated with first line EGFR TKI.
Methods:
Tumors from 90 patients with advanced stage NSCLC with EGFR mutations and treated with first line EGFR TKI were analyzed. Double staining for CD3 and PDL1 was performed by immunohistochemistry. PDL1 expression in tumour membrane, and PDL1 and CD3 expression in tumor and stromal immune cells were segmented and quantified using the Vectra slide imaging system (Perkin Elmer, Waltham, MA).
Results:
The median age of patients was 62 (range 34-88) years, 64 (71%) were female, 69 (77%) were never smokers, and 43 (48%) harbored EGFR exon 19 deletion. Most immune cells were CD3-ve and PDL1-ve in the tumor (median 99%) and stroma (median 86%). PDL1 tumor membrane expression was associated with PDL1 expression in CD3+ve immune in the tumor and stroma. There was no association between PDL1 or CD3 expression with response rate or time to progression.
Conclusion:
This is the first study to characterize PDL1 expression in immune cells in advanced stage NSCLC harboring EGFR mutations. PDL1+ve immune cells are rare in this patient population. PDL1 expression in tumor membrane and immune cells may not be associated with outcome in NSCLC patients harboring EGFR mutations and treated with EGFR TKIs.
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-068 - PD-L1 Expression in Tumor Infiltrating Immune Cells Determined by Digital Imaging Is Associated with Poor Survival in NSCLC Patients (ID 1138)
09:30 - 09:30 | Author(s): Z. Fazreen
- Abstract
Background:
Programmed Death-Ligand 1 (PD-L1) has emerged as a potential prognostic marker and as an effective target for therapeutic inhibition in cancer. Using digital slide imaging, we evaluated the clinical, molecular and survival associations of PD-L1 expression in non-small cell lung cancer (NSCLC) according to cell type (tumor and immune cell) and tissue localization (tumor and stroma).
Methods:
Tumor samples from 199 NSCLC patients were stained for PD-L1 by immunohistochemistry (IHC) and quantitatively assessed using the Vectra slide imaging system for PD-L1 tumor membrane expression (TME), PD-L1 positive (+) tumor immune cell density (TICD) and PD-L1+ stroma immune cell density (SICD). Assessment of gene mutation and anaplastic lymphoma kinase rearrangement were performed using the AmpliSeq Cancer Hotspot V2 assay and IHC, respectively.
Results:
High PD-L1 TME correlated with larger tumor size, squamous cell histology and poor differentiation. PD-L1+ TICD was associated with male gender and wild-type EGFR. Univariate analysis revealed that stage (p=0.001), PD-L1 TME (p=0.007) and PD-L1+ TICD (p=0.006) were associated with worse survival. Iterative p-value analysis indicated the optimal thresholds for PD-L1 TME were 30 (p=0.003, 73% of cases) or 160 (p<0.001, 7%), while for PD-L1+ TICD they were 6.9% (p=0.022, 33%) or 20% (p=0.001, 5%). In multivariate analysis, stage (p=0.018), PD-L1 TME≥160 (p=0.040) and PD-L1+ TICD≥6.9% (p=0.015) were independently associated with survival.
Conclusion:
PD-L1 Tumor Membrane Expression (TME) and PD-L1+ Tumor Immune Cell Density (TICD) expression determined by digital analysis have prognostic value in NSCLC.
